The intestine is an organ with exceptionally high rate of cell turnover and perturbations in this process can lead to disease such as cancer or intestinal atrophy. Nutrition is a key factor regulating the intestinal cell turnover and has a profound impact on intestinal volume and cellular architecture. However, how the intestinal equilibrium is maintained in fluctuating dietary conditions is insufficiently understood. By utilizing the Drosophila midgut as a model, we reveal a novel nutrient sensing mechanism coupling stem cell metabolism with stem cell extrinsic growth signal. Our results show that intestinal stem cells (ISCs) employ the hexosamine biosynthesis pathway (HBP) to monitor nutritional status and energy metabolism. Elevated activity of the HBP promotes Warburg effect-like metabolic reprogramming, which is required for the reactivation of ISCs from calorie restriction-induced quiescence. Furthermore, the HBP activity is an essential facilitator for insulin signaling-induced intestinal growth. In conclusion, intestinal stem cell intrinsic nutrient sensing regulates metabolic pathway activities, and defines the stem cell responsiveness to niche-derived growth signals. Overall design: Intestinal mRNA profiles of 7 days old mated females of UAS-mCD8::GFP, hsFLP; tub-GAL4/+; FRT82B tub-GAL80/FRT82B genotype kept in calorie-restriction +/- 0.1M D-acetylglucosamine for 24h.
Stem Cell Intrinsic Hexosamine Metabolism Regulates Intestinal Adaptation to Nutrient Content.
Sex, Specimen part, Treatment, Subject
View SamplesThe microarray analysis was designed to test the effects of HES5.3 siRNAs, Atoh7 siRNAs and nt siRNAs on gene expression in embryonic chick retina.
A positive feedback loop between ATOH7 and a Notch effector regulates cell-cycle progression and neurogenesis in the retina.
Age, Specimen part
View SamplesYEAST STRAIN:
Excess mannose limits the growth of phosphomannose isomerase PMI40 deletion strain of Saccharomyces cerevisiae.
No sample metadata fields
View SamplesWe attempted to identify alterations in gene expression that occur during the progression from normal breast to ductal carcinoma in situ (DCIS) with the aim to elucidate significant genes and pathways underlying the premalignant transformation. To determine the expression changes that are common to multiple DCIS models (MCF10.DCIS, SUM102 and SUM225) and normal mammary epithelial cells (MCF10A), we grew the cells in three dimensional overlay culture with reconstituted basement membrane and used the extracted RNA for 76 cycles of deep sequencing (mRNA-Seq) using Illumina Genome Analyzer GAIIx. Analysis of mRNA-Seq results showed 295 consistently differentially expressed transcripts in DCIS models as compared to MCF10A. These differentially expressed genes are associated with a number of signaling pathways such as integrin, fibroblast growth factor and TGFß signaling. Many differentially expressed transcripts in DCIS were found to be involved in cell-cell signaling, cell-cell adhesion and cell proliferation. We further investigated ALDH5A1 gene that encodes for the enzyme, aldehyde dehydrogenase 5A1, which is involved in glutamate metabolism. Further, inhibition of ALDH5A1 with different pharmacological drugs resulted in significant inhibition of cell growth and proliferation in the DCIS models. Overall design: Four cell lines examined: normal mammary epithelial cell line (one sample) and three ductal carcinoma in situ cell lines (three samples). Each sample has two duplicates
RNA-Seq of human breast ductal carcinoma in situ models reveals aldehyde dehydrogenase isoform 5A1 as a novel potential target.
Disease, Cell line, Subject
View SamplesThe 6-hydroxydopamine (6OHDA) rat model of parkinsonism is among the first, and most commonly used, animal models of Parkinsons disease. It provides insight into the compensatory changes that occur in the brain after dopamine (DA) neuron degeneration. In order to better define the consequences of substantia nigra DA neuron loss on the neural and glial populations during and following nigrostriatal degeneration, tissue was collected and evaluated from the substantia nigra of 6OHDA or vehicle treated, or nave rats at 1, 2, 4, 6 & 16 weeks.
The longitudinal transcriptomic response of the substantia nigra to intrastriatal 6-hydroxydopamine reveals significant upregulation of regeneration-associated genes.
Sex, Specimen part
View SamplesAluminum toxicity is one of the major limiting factors for many crops worldwide. The primary symptom of Al toxicity syndrome is the inhibition of root growth, leading to poor water and nutrient absorption. The causes of this inhibition are still elusive, with several biochemical pathways being affected and with a significant variation between species. Most of the work done so far to investigate the genes responsible for Al tolerance used hydroponic culture. Here we evaluated plant responses using soil as substrate, which is a condition closer to the field reality.
Transcriptional profile of maize roots under acid soil growth.
Specimen part
View SamplesSpinal muscular atrophy (SMA) is one of the most common inherited forms of neurological disease leading to infant mortality. Patients exhibit selective loss of lower motor neurons resulting in muscle weakness, paralysis, and often death. Although patient fibroblasts have been used extensively to study SMA, motor neurons have a unique anatomy and physiology which may underlie their vulnerability to the disease process. Here we report the generation of induced pluripotent stem (iPS) cells from skin fibroblast samples taken from a child with SMA. These cells expanded robustly in culture, maintained the disease genotype, and generated motor neurons that showed selective deficits compared to those derived from the childs unaffected mother. This is the first study to show human iPS cells can be used to model the specific pathology seen in a genetically inherited disease. As such, it represents a promising resource to study disease mechanisms, screen novel drug compounds, and develop new therapies.
Induced pluripotent stem cells from a spinal muscular atrophy patient.
No sample metadata fields
View SamplesFK1706 potentiated nerve growth factor-induced neurite outgrowth, putatively mediated via FKBP-52 and the Ras/Raf/MAPK signaling pathway. It also improved mechanical allodynia accompanied by the recovery of intraepidermal nerve fiber density in a painful diabetic neuropathy in rats.
FK1706, a novel non-immunosuppressive immunophilin ligand, modifies gene expression in the dorsal root ganglia during painful diabetic neuropathy.
Specimen part, Treatment
View SamplesMaintaining metabolic homeostasis in response to fluctuating nutrient intake requires intricate coordination between tissues of multicellular animals. The insulin/glucagon axis is well known to hormonally coordinate organism-wide carbohydrate metabolism. The ChREBP/Mondo-Mlx transcription factors regulate glycolytic and lipogenic genes locally in hepatocytes and adipocytes, but its role in systemic metabolic homeostasis has remained poorly understood. We demonstrate that Mondo-Mlx controls gene activity in several peripheral tissues of Drosophila melanogaster, where it regulates nutrient digestion and transport as well as carbohydrate, amino acid and lipid metabolism. In addition to directly regulating metabolic genes Mondo-Mlx controls a regulatory network composed of the Activin ligand Dawdle and GLI similar transcription factor Sugarbabe. Dawdle and Sugarbabe contribute to the regulation of a subset of Mondo-Mlx-dependent processes, including sugar-induced de novo synthesis of serine and fatty acids. In summary, our study establishes Mondo-Mlx sugar sensor as a master regulator of organismal metabolic homeostasis upon sugar feeding. Overall design: Control (sug17d/+) and sugarbabe null mutant (sug17d/sug def) third instar larvae were fed control low sugar or high sugar diet and total RNA was extracted from the whole larvae.
Mondo-Mlx Mediates Organismal Sugar Sensing through the Gli-Similar Transcription Factor Sugarbabe.
Specimen part, Subject
View SamplesScope: As a result of population ageing, the number of Alzheimer’s disease (AD) patients has rapidly increased. There are many hypothesises on the pathogenesis of AD, but its detailed molecular mechanism is still unknown, and so no effective preventive or therapeutic measures have been established. Some reports showed a decrease in levels of norepinephrine (NE) has been suspected to be involved in the decline of cognitive function in AD patients and NE concentrations were decreased in postmortem AD patient brains. Tyr-Trp was identified as being the most effective dipeptide in enhancing norepinephrine (NE) synthesis and metabolism. And Tyr-Trp treatment ameliorated the short-term memory dysfunction in AD model mice caused by amyloid beta (Aβ) 25-35. So, the purpose of this study was to investigate the preventive or/and protective effects of Tyr-Trp administration in AD model mice.
Tyr-Trp administration facilitates brain norepinephrine metabolism and ameliorates a short-term memory deficit in a mouse model of Alzheimer's disease.
Specimen part
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